Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the Children's Oncology Group

Abstract

Background: To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV).

Methods: Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS.

Results: A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV-non-NF1 group (P < .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV-treated children without NF1. NF1 patients and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P < .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non-NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV-NF1 group) at a median of 7.8 years (range, 7.3-9.4 years) after enrollment, but there were none in the non-NF1 group.

Conclusions: Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928-36. © 2016 American Cancer Society.

Keywords: carboplatin; childhood low-grade glioma; neurofibromatosis 1; pilocytic astrocytoma; vincristine.

Figure 1

CONSORT diagram. (*) 6 patients died: 2 from progressive/persistent disease, 1 from infection, 1 from hemorrhage, 2 from other/unreported reason. None of the deaths were the first event. (**) 21 patients died: 18 from progressive/persistent disease, 3 from other/unknown reason. The death was the first event in one patient. Patients with discontinued intervention or lost to follow-up were censored at date last seen. Of the 3 patients with SMN, 2 as shown had the SMN as first event.

Figure 2

Event-free survival (EFS) for NF1 and non-NF1 children. NF1 patients had significantly better prognosis than non-NF1 patients in terms of EFS (P<0.001).

Figure 3

The amount of residual tumor as a prognostic factor in NF1 (Fig. 3A) or non-NF1 (Fig. 3B) patients. The EFS outcomes for these 3 groups were significantly different for NF1 patients (Fig. 3A, P=0.02, log-rank trend test P=0.01), but not for non-NF1 patients (Fig. 3B, P=0.18).

Figure 4

Age as a prognostic factor in NF1 (A) or non-NF1 (B) patients. The EFS for the 3 age groups were significantly different for non-NF1 patients (Fig. 4B, P=0.0015, log rank trend test P=0.004), but not for NF1 patients (Fig 4A, P=0.73).